Recently, a sudden death syndrome among Swedish orienteers has been observed. Of approximately 200 elite orienteers six died in myocarditis during 1989–1992 (1). Orienteering, aiming to find the fastest/shortest way between several checkpoints and often in forested areas, is exceptional with respect to environmental exposure. Thus it has been speculated, that the sudden deaths syndrome among orienteers is caused by a vector borne (rodent or arthropod) infectious agent.
It has now been shown in an epidemiological study that the incidence of deaths in myocarditis in northern Sweden tracked the 3–4 year population fluctuations (cycles) of bank voles (Clethrionomys glareolus) with one year time lag. Previously, it has been shown that cardioviruses, with rodents as their natural reservoir, can cause Guillain Barré Syndrome (GBS) in man, Diabetes Mellitus (DM) in mice and myocarditis in several species including non-human primates.
In addition to death in myocarditis it is also shown in the epidemiological study that the number of patients diagnosed with Guillain Barré Syndrome (GBS), and Diabetes Mellitus (DM) in northern Sweden tracked the 3–4 year population fluctuations of bank voles with different time delays.
Sven Gard and co-workers studied antibody prevalence to encephalomyelitis virus (EMCV) in Swedish normal population in the early 1950th (2). These studies found a surprisingly high antibody prevalence rate by hemagglutination inhibition test but no sera could be confirmed by neutralization test. These results were found puzzling at the time but could be explained by the presence of one or several related picornaviruses circulating in Sweden.
The fact that enterovirus have a large number of members and cardiovirus only two possibly three could reflect the true diversity of the two genus or only be the result of the amount of effort made to isolate new viruses from rodents as compared to isolating new enteroviruses from humans.
The Picornavirus family is presently divided into five genera (aphto-, entero-, hepato-, rhino-, and cardioviruses) (3). This taxonomy was initially based on morphological, physiological and serological properties as well as on the pathogenicity of the viruses. More recently, however, viruses have been characterized based on their genome sequence since it has been established that sequence data to a large extent coincide with the characterisation properties used previously (4,5).
The prototype virus in the cardiovirus genus is Theiler's murine encephalomyelitis virus (TMEV). Another member in this genus is encephalomyocarditis virus (EMCV). Vilyuisk virus, isolated from patients in Russia with degenerative neurological disease, is serologically related to TMEV but presently under consideration for being included as a third distinct member of the cardiovirus genus (6).
In nature, cardioviruses have a geographically widespread distribution and a large number of susceptible hosts with rodents as their natural reservoir. In addition to rodents, EMCV has been isolated from domestic pigs, elephants, lions, non human primates and man (7,8,9). Infection with TMEV and EMCV have provided excellent animal models for inducing myocarditis, DM and different neurological disorders such as demyelinating diseases resembling multiple sclerosis in mice (10–16). Other neurological or muscular disorders in which an infection is suspected to be the triggering factor and in which there is also an autoimmune component are Cardiomyopathia, Multiple Sclerosis (MS), Chronic Fatigue Syndrome (CFS), Myasthenia Gravis (MG), and Amyothrophic Lateral Sclerosis (ALS). It has never been established, however, that cardiovirus is a significant human pathogen, as disease in man most often has been described in case reports or as infection measured in sero-epidemiological surveys (7–17).
Thus, there may be other not yet identified picornaviruses circulating in the wild rodent population and occasionally infecting humans resulting in Myocarditis, Cardiomyopathia, Guillain Barré Syndrome, and Diabetes Mellitus, Multiple Sclerosis, Chronic Fatigue Syndrome, Myasthenia Gravis, Amyothrophic Lateral Sclerosis, Dermatomyositis, Polymyositis, Spontaneous Abortion, and Sudden Infant Death Syndrome, in genetically susceptible individuals.
The epidemiological link between important human diseases and small rodent abundance and what is previously known about picornavirus/cardiovirus motivated attempts to isolate novel picornaviruses from small rodents.